Embryonic stem (ES) cells have the ability to give rise to all cell types, including germ lines (pluripotent), and the ability to undergo an unlimited number of symmetrical divisions without differentiation (self-renewal). For potential therapeutic applications of stem cells, it is paramount to understand how the ES cells maintain their pluripotency and self-renewal, and how the ES cells differentiate into specific cell lineages in vitro. The goal of this research project is to understand the relevant nature of mouse embryonic and tissue stem cells, and to identify genes that are responsible for the maintenance of cellular pluripotency. In our earlier work, we compared the global expression profiles of mouse ES cells and trophoblast stem (TS) cells by DNA microarrays. We studied Esg1, one of the genes identified as a gene expressed specifically in ES cells, and found that the gene encodes an RNA-binding protein that binds to many RNA targets (Tanaka et al., 2006). We have also compared the expression profiles of mouse ES cells undergoing neural differentiation in vitro and those of adult neural stem/progenitor (NS) cells (Aiba et al., 2006). The results suggested that ES cells undergoing neural differentiation in vitro recapitulate the development of neural lineages in vivo. We also found a set of ~4,000 genes, the expression of which increased with neural commitment/differentiation and can be used as a scale for the degree of commitment/differentiation in neural differentiation. We are extending these studies by carrying out global gene expression profiling of mouse embryonic germ (EG) cells and multipotent adult stem cells (MAPCs).